key: cord-260923-hwvtxy9g authors: Jain, Amit; Lamperti, Massimo; Doyle, D. John title: Dexmedetomidine: another arrow in the quiver to fight COVID-19 disease in intensive care units date: 2020-10-14 journal: Br J Anaesth DOI: 10.1016/j.bja.2020.10.010 sha: doc_id: 260923 cord_uid: hwvtxy9g nan While dexmedetomidine-mediated improvements in hypoxic pulmonary vasoconstriction and ventilation-perfusion ratios were proposed explanations for improved oxygenation following dexmedetomidine administration in COVID-19 patients, 12 dexmedetomidine's anti-inflammatory properties may also be instrumental in reducing disease severity. Such properties include favorable alterations of inflammation and immune function either directly via cell surface receptors or indirectly by altering sympathetic/parasympathetic imbalance. 7 There are several putative mechanisms by which dexmedetomidine might be advantageous in COVID-19 patients Hypoxia inducible factor-1α (HIF-1α) induced changes in monocyte metabolism by SARS-CoV-2 infection has been identified to inhibit T-cell response directly and reduce epithelial cell survival. 22 As, dexmedetomidine can suppress mitochondrial reactive oxygen species formation and inhibit HIF-1α dependent glycolysis in preclinical settings, 23 we believe that early use of A novel role for lidocaine in COVID-19 patients? Effect of sedation with dexmedetomidine versus lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial Sedation of mechanically ventilated adults in intensive care unit: a network meta-analysis Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome COVID-19 and the nicotinic cholinergic system Dexmedetomidine and worsening hypoxemia in the setting of COVID-19: A case report Potential therapeutic value of dexmedetomidine in COVID-19 patients admitted to ICU Dexmedetomidine protects against high mobility group box 1-induced cellular injury by inhibiting pyroptosis Dexmedetomidine Preconditioning Protects Cardiomyocytes Against Hypoxia/Reoxygenation-Induced Necroptosis by Inhibiting HMGB1-Mediated Inflammation Effects of Dexmedetomidine Infusion on Inflammatory Responses and Injury of Lung Tidal Volume Changes during One Lung Ventilation in Thoracoscopic Surgery: A Randomized Controlled Trial Dexmedetomidine regulates inflammatory molecules contributing to ventilator-induced lung injury in dogs The dose-related effects of dexmedetomidine on renal functions and serum neutrophil gelatinase-associated lipocalin values after coronary artery bypass grafting: a randomized, triple-blind, placebo-controlled study The influence of dexmedetomidine and propofol on circulating cytokine levels in healthy subjects TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis NFκB and JAK/STAT signaling pathways as well as activation of cholinergic pathways confer antiinflammatory and organ-protective effects and may reduce oxidative-stress mediated pyroptosis and thrombotic complications of COVID-19 disease. Dexmedetomidine inhibits mitochondrial ROS (mt-ROS), and may thereby prevent SARS-CoV-2 triggered mt-ROS production and stabilization of HIF-1α and consequent sustained aerobic glycolysis mediating cytokine storm and inflammation RAGE: receptors for advanced glycation end-products, TLR: Toll-like receptor, ROS: reactive oxygen species, Cit. H3 histone: citrullinated H3 histone, MPO: myeloperoxidase, NE: neutrophil elastase, LL-37: cathelicidin antimicrobial peptide, HMGB1: high mobility group box-1, DAMP: damage-associated molecular pattern, PAMP: pathogen associated molecular pattern, PRR; pattern recognition receptor, MAVS: mitochondrial antiviral-signaling protein